This will be the fifth year of a continuing study intending to define various inbred strains of Syrian hamsters (Mesocricetus auratus auratus) with respect to their responses to various types of carcinogens administered by various routes. Significant differences in the response of more than 12 inbred Syrian hamsters to subcutaneous and intragastric administration of polycyclic hydrocarbons (specifically, methyl-cholanthrene by stomach tube, benzo(a)pyrene, methylcholanthrene and dimethylbenzanthracene by s.c. injection in glyceryl trioctanoate ("tricaprylin") have been demonstrated and published. We intend now to study the mechanisms responsible for these differences by genetic studies (F1, F2, appropriate backcrosses) and to examine, where possible, the molecular basis for the observed differences. This will include the measurement of the Michaelis constant for aryl hydrocarbon hydroxylase in hepatic microsomes in susceptible and resistant strains: constitutive and induced aryl hydrocarbon hydroxylase activities will be compared in carcinogen resistant and in susceptible segments of gut and colon in males, with the resistant female colons of the same BIO 15.16 strain serving as controls. Attempts will be made to develop transplantable tumor lines of various types from the carcinogen-induced neoplasms and to carry such tumors in cheek pouches of syngeneic inbred hamsters. The low spontaneous tumor incidence observed in old inbred Syrian hamsters lends this project special practical importance since the discovery of environmental carcinogens requires susceptible animals with the lowest possible incidence of spontaneous neoplasms. Markedly shortened latency periods in hybrids of susceptible lines promise better experimental models of environmental carcinogenesis.